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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 73 records · Page 4Linked to original sources

Clostridium difficile diarrhea and colonization after treatment with abdominal infection regimens containing clindamycin or metronidazole.

One hundred fifty-six patients with presumed or documented abdominal infections were treated with amikacin/metronidazole/placebo (Group 1, 56 patients), amikacin/clindamycin/placebo (Group 2, 57 patients), or amikacin/clindamycin/ampicillin (Group 3, 43 patients) to determine both the therapeutic efficacy of the various regimens and the type of complications due to Clostridium difficile. C. difficile diarrhea occurred in 15 of 156 patients (9.6%), and C. difficile colonization occurred in 14 of 156 patients (9%) during treatment and 30 days of follow-up. The number of C. difficile diarrhea cases in Group 1 (3 of 56) was significantly lower than in Group 2 (9 of 57, p less than 0.05), but not in Group 3 (3 of 43). Exclusion of all patients who received other antibiotics in the 30-day poststudy period revealed no C. difficile diarrhea or colonization in Group 1 (0 of 13) and an acquisition rate of 31% (14 of 45) with the regimens containing clindamycin (p less than 0.02). Successful treatment outcomes (106 evaluable patients) were not statistically different among the three groups (Group 1, 64%; Group 2, 76%; and Group 3, 88%), but these data were difficult to interpret because, by chance, significantly more patients in Group 1 had bacteremia at entry (p less than 0.01), and patients in Group 3 had significantly more biliary tract infections (p less than 0.02) and significantly more favorable acute physiology scores (p less than 0.05). Use of metronidazole can reduce complications related to C. difficile, particularly if additional antimicrobials other than aminoglycosides are avoided.

Abdomen↗

In vitro activity of LY 264826 compared with that of vancomycin against 100 clinical isolates each of methicillin-resistant Staphylococcus aureus and Clostridium difficile.

The in vitro activity of LY 264826, a new glycopeptide antibiotic, was compared with that of vancomycin against 100 strains each of methicillin-resistant Staphylococcus aureus and Clostridium difficile. LY 264826 was more active, by weight, than vancomycin against the isolates tested. The human serum protein binding of LY 264826 was 15.3% (range, 9.8 to 21.8%).

Anti-Bacterial Agents↗

Treatment evaluation of experimental staphylococcal infections: comparison of beta-lactam, lipopeptide, and glycopeptide antimicrobial therapy.

LY 146032, teicoplanin, vancomycin, oxacillin, cephalothin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam were studied against six isolates of staphylococci (including both Staphylococcus aureus and coagulase negative staphylococci) using in vivo and in vitro methods. In vitro susceptibility measurements demonstrated that all six isolates were sensitive to LY 146032 and vancomycin and that five of six isolates were sensitive to tiecoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam. Comparison of antimicrobial therapy in an in vivo rabbit model demonstrated that cefoperazone plus sulbactam was active against the greatest number of isolates (five of six) based on a reduction of greater than or equal to 5.0 log10 colony forming units per milliliter (CFU/ml) from growth control at the end of the animal treatment study. Vancomycin and oxacillin were equal in achieving reductions of greater than or equal to 5.0 log10 CFU/ml in four of the six isolates. Comparing each isolate's in vivo outcome to in vitro data shows that in vitro susceptibility tests overpredict the sensitivity of these six isolates to LY 146032 and vancomycin, are variable for teicoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam, and underpredict for oxacillin.

Ampicillin↗

Comparative efficacy of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole, and penicillin G against anaerobic bacteria in an animal model.

Treatment efficacy of various antimicrobial regimens against anaerobes was studied in semipermeable chambers simulating a closed-space, locally neutropenic infection site in rabbits. Bacteroides fragilis, Bacteroides melaninogenicus, Clostridium perfringens, and Peptostreptococcus anaerobius were inoculated (at a mean of 5.3 log10 CFU/ml in prereduced pooled rabbit serum) into the chambers (one isolate per chamber) in triplicate. Antimicrobial therapy consisted of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole (against the gram-negative anaerobes), or penicillin G (against the gram-positive anaerobes), beginning 4 hours after organism inoculation and continuing every 6 hours for 16 doses. With the use of anaerobic techniques for specimen acquisition, transport, and culture, quantitative bacterial findings were measured at the start of therapy and at various time points thereafter. Antibiotic concentrations were measured in blood and chamber fluid by liquid chromatography or bioassay methods. At the end of the study in vivo organisms were reduced by at least 3 log10 CFU/ml from drug-free growth control chambers by all the antimicrobial regimens tested except for cefoperazone against B. fragilis and ciprofloxacin against the three isolates tested. The addition of sulbactam to cefoperazone inhibited B. fragilis beta-lactamase activity and eradicated B. fragilis in vivo. In vivo results with this model confirmed in vitro susceptibilities of all tested antimicrobials except ciprofloxacin and should provide useful indications of the potential clinical efficacy of other new agents against anaerobes.

Animals↗

Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization.

We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment.

Anti-Bacterial Agents↗

Effects of biliary obstruction on hepatic clearance of bacteria.

High surgical mortality in patients with obstructive jaundice and sepsis have been attributed to reticuloendothelial system (RES) depression. The purpose of this study was to clarify the effects of mechanical biliary obstruction on RES clearance of pathogenic bacteria by comparing the phagocytic index (K) with the directly measured hepatic uptake of indium 111-labeled bacteria injected into the portal vein of normal dogs and dogs with partial (PBO) or complete biliary obstruction (CBO). No significant difference was observed between the K in normal dogs (0.19 +/- 0.08; n = 6) and that in dogs with PBO (0.24 +/- 0.06; n = 5) or CBO (0.21 +/- 0.03; n = 4). There was no significant difference in uptake of radiolabel by the liver among the three groups of dogs. In our model, biliary obstruction had no effect on hepatic RES function and may not represent a significant determinant of mortality in patients with obstructive jaundice.

Alkaline Phosphatase↗

Therapy of lower extremity infections with ciprofloxacin in patients with diabetes mellitus, peripheral vascular disease, or both.

PURPOSE: Lower extremity infections in the presence vascular insufficiency are difficult and costly to treat. Few well-controlled clinical trials evaluating the management of these infections exist. We decided to investigate the ability of a new fluoroquinolone, ciprofloxacin, to reduce the morbidity associated with these infections and the amount of in-hospital time required for the administration of antibiotic therapy. PATIENTS AND METHODS: Forty-eight patients with peripheral vascular disease (46 with diabetes mellitus) who presented to the hospital for treatment of lower extremity infections were randomized in a blinded fashion to receive oral ciprofloxacin at a dosage of either 750 mg or 1,000 mg twice daily. Patients with osteomyelitis received three months of therapy and those with infections limited to soft tissues, three weeks of ciprofloxacin treatment. All subjects were followed for one year. RESULTS: One patient received an amputation 24 hours after enrollment, and two patients discontinued therapy after 20 and 34 days because of adverse effects and were not evaluable. At the one-year follow-up, 27 of the 45 (60 percent) evaluable patients had a fully successful outcome defined as not requiring either repeat antimicrobial therapy for their initial infection or amputation of the involved extremity. In the group of 18 patients in whom therapy failed, a total of only nine amputations were required. In the 15 patients whose lesion closed during therapy, 93% (14 patients) experienced a long-term successful outcome. CONCLUSION: Treatment with this new fluoroquinolone offers promise for the improved outcome of patients with the serious infectious complication of infected lower extremity ulcerations in peripheral vascular disease, diabetes mellitus, or both.

Adult↗

Influence of protein binding on therapeutic efficacy of cefoperazone.

The effect of protein binding of cefoperazone (89.3% bound to rabbit serum) on antibacterial activity in serum was tested in a model that simulated a closed-space infection in a neutropenic host. Four gram-negative bacilli were tested in the model with cefoperazone doses of 20 and 200 mg/kg administered intramuscularly every 6 h for 16 doses. Cefoperazone efficacy was measured at 92 h by determining the log10 decrease in bacterial count from that of the control for five paired studies with three isolates. A significantly better response was demonstrated when the free (non-protein-bound) drug concentration exceeded the MICs and MBCs for the infecting microorganisms at the infection site at all times (P less than 0.005). This supports the concept that free (unbound) drug is the active component in treating bacterial infections.

Animals↗

Detection of asymptomatic Clostridium difficile carriage by an alcohol shock procedure.

Direct inoculation to cefoxitin-cycloserine-fructose agar and broth was compared with alcohol shock-chopped meat broth inoculation for optimal detection of Clostridium difficile in fecal samples. Alcohol shock is significantly more sensitive than cefoxitin-cycloserine-fructose agar or broth and may be the method of choice to detect C. difficile in asymptomatic carriers.

Bacteriological Techniques↗

Neutrophil chemotaxis and adherence in vitro and localization in vivo in rabbits with Staphylococcus aureus abscesses.

Decreased neutrophil (PMN) function may contribute to an altered host defense system in hosts with bacterial abscesses but has not been well correlated to in vivo outcome. We have found that blood PMNs from rabbits with chronic (2-week) experimental Staphylococcus aureus abscesses have decreased chemotaxis in response to an S. aureus supernatant (370 +/- 130 microns migration vs 570 +/- 180 microns, p less than 0.05) and decreased adherence (11.5% +/- 13.2% vs 32.9% +/- 18.6%, p less than 0.005) compared with PMNs from animals with acute (24-hour) abscesses. No differences were found in chemokinesis, random migration, and chemotaxis in response to zymosan-activated serum. No plasma inhibitors of PMN chemotaxis or inhibitors of chemotaxins were found. Although animals with chronic abscesses had higher levels of circulating chemotaxins, in both groups of animals abscess chemotaxin levels were greater than the plasma chemotaxin level. Animals with a concomitant chronic abscess had less PMN influx into an acute abscess but also less bacterial growth within the abscess than animals without a concomitant chronic abscess. We conclude that rabbits with chronic staphylococcal abscesses have decreased chemotaxis and adherence measured in vitro and decreased PMN localization in vivo. In this model, these functions were not associated with increased bacterial proliferation in vivo.

Abscess↗

Nosocomial febrile illnesses in patients on an internal medicine service.

Febrile illnesses commonly arise in hospitalized patients after admission, but most previous studies have been of specific subsets of febrile illnesses. To provide practical information about the problem as a whole, we studied febrile illnesses arising after admission (nosocomial febrile illnesses [NFls]) in 123 inpatients of an internal medicine service who had been afebrile for the preceding week. We compared them with 123 randomly selected patients without NFl. Causes of NFl included infections in 83 cases; noninfectious, inflammatory states in 15; malignancy in 12; ischemia in eight; and procedures in three. Evidence for the cause of the NFl was present at onset in at least 110 of the 123 patients. Despite this, antimicrobial agents were administered to 23 (58%) of 40 patients without infections. Thirty-four patients with NFl died; the NFl contributed to death in 26. In contrast, only eight comparison patients died. "Do not resuscitate" status was present in 32 patients with NFl compared with only 12 comparison patients, and 19 (59%) of the former died. The data from this study provide a comprehensive description of NFl arising in hospitalized internal medicine patients, indicate that the occurrence of a new febrile illness signifies a poor prognosis, and provide a rational basis for management.

Catheterization, Central Venous↗

Results of a prospective, 18-month clinical evaluation of culture, cytotoxin testing, and culturette brand (CDT) latex testing in the diagnosis of Clostridium difficile-associated diarrhea.

An 18-mo evaluation of culture, cytotoxin, and latex testing for Clostridium difficile was performed between July 1, 1985, and December 31, 1986, on 1,536 specimens from 1,406 patients during evaluation of diarrhea. All cases with at least one test positive were investigated for clinical status. There were 144 Clostridium difficile-associated diarrhea (CAD) patients; 139 (97%) were positive by culture, 96 (67%) by cytotoxin, and 98 (68%) by latex testing. In the 1,262 non-CAD patients with diarrheal stool, 89 (7.1%) were positive by culture, 18 (1.4%) by cytotoxin, and 68 (5.4%) by the latex test. No CAD patient was positive by cytotoxin testing only, and two were positive by latex testing only. The culture and cytotoxin positivity were similar to our previous reports of 90-97% and 70-73%, respectively. Latex sensitivity (68%) was comparable to that of cytotoxin testing in this large group of patients (p greater than 0.5). Overall, in the 1,262 patients without clinical evidence of Clostridium difficile disease, positive tests by latex testing (5.4%) were intermediate between those of culture (7.1%, p less than 0.1) and cytotoxin (1.4%, p less than 0.001).

Bacteriological Techniques↗

Characterization of a nosocomial Clostridium difficile outbreak by using plasmid profile typing and clindamycin susceptibility testing.

The mean number of cases of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center increased to 17.3 per month in June-August 1985, compared with 7.1 per month in the previous 17 mo. Plasmid profiles and clindamycin susceptibility were used as markers to evaluate the increase in cases. Ninety clindamycin-resistant and 22 clindamycin-susceptible isolates of C. difficile from 1985 were examined for plasmids. A clindamycin-resistant organism contained a cryptic plasmid of 3.1 kilobases (kb). None of the clindamycin-susceptible isolates contained the 3.1-kb plasmid, as compared with 40 of 90 clindamycin-resistant isolates (P less than .005). Restriction endonuclease digestion and Southern blot hybridization were used to confirm the identity of the 3.1-kb plasmid between strains. Isolates retained clindamycin resistance after plasmid curing. It could not be determined if the organism responsible was an indigenous C. difficile strain that acquired a plasmid or was a new strain introduced from outside the hospital.

Bacterial Toxins↗

Immunoblots and plasmid fingerprints compared with serotyping and polyacrylamide gel electrophoresis for typing Clostridium difficile.

Two new methods for typing Clostridium difficile, immunoblotting and plasmid fingerprinting, were compared with serotyping and polyacrylamide gel electrophoresis (PAGE). Of these methods, immunoblotting was found to be the most valuable for use in a comprehensive typing system. More groups could be distinguished by immunoblotting than by serotyping or PAGE. Immunoblotting results were also more reproducible and distinctive than results by PAGE. Plasmid fingerprinting was an excellent marker for plasmid-bearing strains, but it had limited use because many isolates lacked plasmids. A unique plasmid profile observed for one group of isolates correlated with differences in phenotypic characteristics resolved by immunoblot analysis but not by serotyping or PAGE. Preliminary attempts to correlate typing results with pathogenicity of isolates were not successful but underscored the need for future studies to include careful assessment of the clinical significance of isolates.

Bacterial Proteins↗